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J Reed

Publications and source records attributed to J Reed.

At least 127 records · Page 7Linked to original sources
PubMed1991

Human and rodent sequence analogs of Alzheimer's amyloid beta A4 share similar properties and can be solubilized in buffers of pH 7.4.

The filamentous amyloid protein aggregates found in the brain of patients affected with Alzheimer's disease principally consist of a peptide termed beta A4, according to its secondary structure of beta-pleated sheets and its molecular mass of about 4 kDa. It has a length of up to 42 or 43 residues. By chemical means, we have synthesized peptide analogs corresponding to the human and rodent beta A4 sequences. We describe structural and functional properties of peptides spanning residues 1-43, 10-23, 1-27 and 4-27 of beta A4. The peptides have been tested for their ability to form filaments in vitro. Their solubilities and secondary structures in solution and in the solid state have been used to detect differences between the properties of human and rodent beta A4 sequences. We show that mouse and rat beta A4 homologs are as amyloidogenic as the human sequence. The absence of amyloid deposits in the brain of aged rats and mice is therefore not due to the three amino acid substitutions identified within the sequence which is homologous to beta A4 of humans. Moreover, peptides corresponding to residues 1-27 of human and rodent beta A4 are solubilized under physiological conditions; thus they are very unlikely to form stable filaments in vivo.

Amino Acid Sequence↗
PubMed1991

A conformational switch is associated with receptor affinity in peptides derived from the CD4-binding domain of gp120 from HIV I.

A 15-residue region within the CD4-binding domain of gp120 from HIV I was identified with use of folding algorithms as conserving the potential for forming a particular secondary structure throughout 11 sequenced HIV strains. The region chosen has a potential for forming both beta-sheet and alpha-helix; the helical form would be amphipathic with the five hydrophobic residues all totally or functionally conserved. Five peptides were synthesized corresponding to this region in strain LAV and the strain most highly divergent from it in primary structure (Z3) plus three additional peptides with critical substitutions in the LAV sequence. The conformation of these five peptides was examined under various conditions with circular dichroism, and the results were compared with the ability of each peptide to bind to a CD4-expressing strain of HeLa cells (HeLa T4). In solution, the unmodified peptides exhibit a bistable structure, existing as beta-sheet in dilute buffer and converting to alpha-helix under more apolar conditions. The transition is reversible and sharp, occurring at a particular point in the polar/apolar gradient with virtually no intermediate state. The ability to undergo this bistable flip is closely associated with binding ability, amino acid substitutions that eliminate binding ability also eliminating the switch, and vice versa. The transition thus may reflect conformational changes occurring in this region of gp120 as it binds to the CD4 receptor.

Algorithms↗
PubMed1991

Aggregation and secondary structure of synthetic amyloid beta A4 peptides of Alzheimer's disease.

The deposition of amyloid beta A4 in the brain is a major pathological hallmark of Alzheimer's disease. Amyloid beta A4 is a peptide composed of 42 or 43 amino acid residues. In brain, it appears in the form of highly insoluble, filamentous aggregates. Using synthetic peptides corresponding to the natural beta A4 sequence as well as analog peptides, we demonstrate requirements for filament formation in vitro. We also determine aggregational properties and the secondary structure of beta A4. A comparison of amino-terminally truncated beta A4 peptides identifies a peptide spanning residues 10 to 43 as a prototype for amyloid beta A4. Infrared spectroscopy of beta A4 peptides in the solid state shows that their secondary structure consists of a beta-turn flanked by two strands of antiparallel beta-pleated sheet. Analog peptides containing a disulfide bridge were designed to stabilize different putative beta-turn positions. Limited proteolysis of these analogs allowed a localization of the central beta-turn at residues 26 to 29 of the entire sequence. Purified beta A4 peptides are soluble in water. Size-exclusion chromatography shows that they form dimers that, according to circular dichroism spectroscopy, adopt a beta-sheet conformation. Upon addition of salts, the bulk fraction of peptides precipitates and adopts a beta-sheet structure. Only a small fraction of peptides remains solubilized. They are monomeric and adopt a random coil conformation. This suggests that the formation of aggregates depends upon a hydrophobic effect that leads to intra- and intermolecular interactions between hydrophobic parts of the beta A4 sequence. This model is sustained by the properties of beta A4 analogs in which hydrophobic residues were substituted. These peptides show a markedly increased solubility in salt solutions and have lost the ability to form filaments. In contrast, the substitution of hydrophilic residues leads only to small deviations in the shape of filaments, indicating that hydrophilic residues contribute to the specificity of interactions between beta A4 peptides.

Alzheimer Disease↗
PubMed1991

Interleukin 2 induces tyrosine phosphorylation and activation of p72-74 Raf-1 kinase in a T-cell line.

Interleukin 2 (IL-2) is a lymphokine, produced by T cells upon antigenic or mitogenic stimulation, that is a critical regulator of T-cell proliferation. Although the binding of IL-2 to its receptor has been well characterized, the molecular mechanisms by which IL-2 transmits its signal from the membrane to the interior of the cell are poorly understood. Like most other growth factors, IL-2 causes rapid phosphorylation of proteins within its target cells. Unlike many other growth factors, however, the known subunits of the IL-2 receptor lack tyrosine-specific kinase activity, and little is known about the kinases whose activities are regulated by IL-2. Here we show that IL-2 (but not IL-4) induces rapid phosphorylation of the p72-74 serine/threonine-specific kinase encoded by the c-Raf-1 protooncogene in an IL-2-dependent murine T-cell line, CTLL-2, and that this phosphorylation is associated with increased kinase activity in p72-74 Raf-1-containing immune complexes. The concentration dependence of IL-2-mediated elevations in Raf-1 kinase activity correlated well with IL-2-stimulated proliferation of CTLL-2 cells. Furthermore, much of the IL-2-stimulated phosphorylation of p72-74 Raf-1 occurred on tyrosines. To our knowledge, the Raf-1 kinase represents the first endogenous substrate of an IL-2-regulated tyrosine kinase to be identified.

Amino Acid Sequence↗
PubMed1991

Clostridium difficile--a common and costly colitis.

Clostridium difficile infection manifests as a self-limiting diarrhea, protracted colitis, or toxic pseudomembranous colitis. The incidence of C. difficile in a 514-bed community hospital was studied retrospectively; 155 patients of a total 18,262 admitted during 1988 were identified with C. difficile as an admitting or subsequent diagnosis. The method of diagnosis, mode of therapy, and related costs were analyzed. We have determined that education, with an emphasis on pathogenesis and prevention, is necessary to reduce the incidence in the hospital and the cost to the patient.

Adult↗
PubMed1991

Development of a novel EEG rating scale for head injury using dichotomous variables.

We developed a new EEG rating scale for electrographic assessment of head injured patients. Phenomena present in posttraumatic EEG were scored as dichotomous variables (present or absent). These phenomena included background activity (alpha, beta, theta, delta), sleep spindles, focal abnormalities, reactivity and variability, epileptiform activity, and specific comatose patterns. Each variable was weighted according to its perceived prognostic value: i.e., normal alpha 10, flat EEG -10, spindles 4, etc. Combinations of possible scores ranged from +23 to -10. Fifty-seven EEGs from different head injured patients were independently and retrospectively analyzed by two investigators. There was a high correlation for intra- (r = 0.95) and inter- (r = 0.85) observer rating using the dichotomous test. When patients with scores over 15 (i.e., with reactive alpha) and patients with scores of -10 (i.e., ECI records) were excluded, the intra-rater and inter-rater correlations were still high (0.81 and 0.76, respectively). There was a high correlation between Glasgow outcome score at discharge and the dichotomous EEG score. This EEG scale scores most major categories of EEG activity, utilizes a multipoint scale for correlation purposes, and allows data to be analyzed in sub-categories (i.e., spindles in coma). The separate weighting score allows for refinement of the scale after data collection (i.e., to fit prospective outcome). We feel that this scale is reproducible and valid, and may be applicable to other patient groups with severely altered EEGs.

Adolescent↗
PubMed1991

Nurses' assessment of elderly patients in hospital.

Nurses' assessment of patients' mobility in hospital provided the focus for an inductive qualitative study which examined how an everyday aspect of nursing practice was carried out. The study described assessment practices in both long-term care and acute care wards for elderly patients as a situated activity. Interviews with nurses, as well as observation of their activities and records, resulted in explanations of their behaviour as deriving from their conceptions of ward functions. These conceptions arose from their adoption of the values of cure and discharge and so, in the different types of ward, assessment held different meanings and was carried out in different ways. The findings have implications for nursing practice in different settings but also for the care of elderly and chronically ill patients, where cure is an inappropriate end goal of care. This example of developing explanatory theory inductively also has implications for the development of mid-range nursing theory and suggestions are made for its extension.

Geriatric Nursing↗
PubMed1991

Psychometric assessment of psychiatric disorders in people with learning difficulties (mental handicap): a review of measures.

Instruments designed to assess psychiatric disorders in people with learning difficulties (mental handicap) were critically reviewed from a psychometric perspective. Major trends were found in the assessment of psychopathology related to DSM-III and depressive disorders although research in other areas was patchy. Although some psychometrically sophisticated measures were identified the area was characterized by an absence of important psychometric data for many measures. Future research should attend to developing assessments of schizophrenia, psycho-sexual disorders, adjustment disorders and the validation of screening procedures and instrument formats. Future studies should include more people with severe and profound learning difficulties.

Humans↗
PubMed1991

Rhizobium meliloti exopolysaccharides: genetic analyses and symbiotic importance.

Genetic experiments have indicated that succinoglycan (EPS I), the acidic Calcofluor-binding exopolysaccharide, of the nitrogen-fixing bacterium Rhizobium meliloti strain Rm1021 is required for nodule invasion and possibly for later events in nodule development on alfalfa and other hosts. Fourteen exo loci on the second megaplasmid have been identified that are required for, or affect, the synthesis of EPS I. Mutations in certain of these loci completely abolish the production of EPS I and result in mutants that form empty Fix- nodules. We have identified two loci, exoR and exoS, that are involved in the regulation of EPS I synthesis in the free-living state. Certain exo mutations which completely abolish EPS I production are lethal in an exoR95 or exoS96 background. Histochemical analyses of the expression of exo genes during nodulation using exo::TnphoA fusions have indicated that the exo genes are expressed most strongly in the invasion zone. In addition, we have discovered that R. meliloti has a latent capacity to synthesize a second exopolysaccharide (EPS II) that can substitute for the role(s) of EPS I in nodulation of alfalfa but not of other hosts. Possible roles for exopolysaccharides in symbiosis are discussed.

Genes, Bacterial↗
PubMed1991

Nerve root recovery in complete injuries of the cervical spine.

Thirty-six patients with complete quadriplegia were reviewed. Twenty-two underwent surgery, and 14 did not. There were 11 burst fractures and 3 extension fracture-dislocations, which were treated with anterior decompression and rigid plate fixation. There were 22 flexion injuries that were treated with posterior stabilization using Kirschner-wire tension band fixation, Harrington compression hooks, or Halifax laminar hooks. The non-operative group was treated with skeletal traction with skull tongs for 6-12 weeks followed by the application of a hard collar or halo vest for 3 months. Of the 22 patients who underwent surgery, 32% descended one level and 18% two levels. In the nonoperative group, only one patient descended one level. It is concluded that the heretofore pessimistic outlook regarding complete quadriplegia is unwarranted and that a more aggressive approach may result in a better functional outcome.

Adolescent↗
PubMed1991

Models of nursing: their relevance to the care of elderly people.

The adoption of nursing models has become widespread throughout the profession with little empirical evidence of their usefulness or critical evaluation. This paper gives an overview of the issues surrounding the development and use of models and presents research data which indicates that one model (Roper, Logan & Tierney's Activities of Living) is problematic in the long-term care of the elderly. The characteristics of this model which are problematic are common to other models and have relevance for other areas of nursing.

Activities of Daily Living↗
PubMed1991

Staff perceptions of sadness among people with mental handicaps.

This study investigated the use of an informant behaviour checklist to examine carestaff perceptions of sadness among a hospital population of people with mental handicaps. Using Cohen's kappa statistic there were only three checklist items which had acceptable levels of inter-rater agreement (physical aggression, crying and verbal abuse) with no significant variation in the incidence of those behaviours according to the severity of mental handicap. The findings suggest that future research might attend to concepts of sadness among carestaff and their ability to identify sad emotional states in a reliable manner.

Adolescent↗
PubMed1991

Nursing diagnosis in the North Carolina public health system: a statewide project.

A group of North Carolina public health nursing leaders initiated a two-phase process of providing a continuing education module on nursing diagnosis for all public health nurses in the state. In the first phase the authors developed the module to teach the skill of nursing diagnosis and evaluation tools, and statewide workshops were held to teach public health nurse administrators and nurse consultants how to use it with their staffs. Results of the evaluation revealed a significant increase in cognitive learning and a more positive attitude overall toward nursing diagnosis among 148 participants. Written comments revealed two major concerns for using nursing diagnoses: the need for additional practice, and charting issues. Both were addressed in this project. Phase two, in which administrative nurses are using the module to teach nursing diagnoses to their staffs, is under way.

Adult↗
PubMed1991

Factors influencing outcome of prednisone dose reduction in myasthenia gravis.

We reviewed retrospectively 114 prednisone dose reduction attempts in 63 myasthenic patients. Dose reduction was considered successful if a patient remained asymptomatic for more than 1 year on no prednisone or a stable low dose of prednisone. Successful dose reduction attempts were more common in patients taking azathioprine, but thymectomy did not influence taper outcome. Slower rate of dose reduction and higher ending dose of prednisone improved the chance of success.

Adolescent↗
PubMed1990

Tuberculosis surveillance in the South Australian aboriginal community.

Tuberculosis (TB) is still a significant problem in Aboriginal people. There are higher rates of active TB and evidence of continuing transmission among this group. We sought to define the specific epidemiological risks and best methods of surveillance for TB in Aboriginal people in South Australia. We compared the incidence of active TB in Aboriginal people in South Australia with that of the total number of cases in non-Aboriginal people from 1978 to 1988, and studied the prevalence of infection in four Aboriginal communities in South Australia. Incidence rates of active TB were four times higher in South Australian Aboriginal people than the total South Australian rates. Specific age analysis revealed higher active disease notification rates in Aboriginal people aged 45-54 years and 55-64 years. The notification rate for Aboriginal men was almost three times the rate for women. Standardized incidence ratios of active TB cases for Aboriginal communities were higher in rural and traditional communities than in urban Aboriginal people. Infection prevalence, measured by tuberculin skin testing, varied from 7.7% to 30.8% in the different communities but did not correlate with the standardized incidence ratios. We conclude that (i) South Australian Aboriginal people are suffering a higher rate of active TB disease than the total South Australian community, and (ii) that the disease and infection rates vary between communities and between age and sex groups. The discrepancy between disease notifications rates, as measured by standardized incidence ratios, and infection prevalence requires further investigation. To improve TB control in Aboriginal people, programmes need to be altered to be more appropriate for this group.

Adolescent↗
PubMed1990

Chaperonin-facilitated refolding of ribulosebisphosphate carboxylase and ATP hydrolysis by chaperonin 60 (groEL) are K+ dependent.

Both the chaperonin- and MgATP-dependent reconstitution of unfolded ribulosebisphosphate carboxylase (Rubisco) and the uncoupled ATPase activity of chaperonin 60 (groEL) require ionic potassium. The spontaneous, chaperonin-independent reconstitution of Rubisco, observed at 15 but not at 25 degrees C, requires no K+ and is actually inhibited by chaperonin 60, with which the unfolded or partly folded Rubisco forms a stable binary complex. The chaperonin-dependent reconstitution of Rubisco involves the formation of a complex between chaperonin 60 and chaperonin 10 (groES). Formation of this complex almost completely inhibits the uncoupled ATPase activity of chaperonin 60. Furthermore, although the formation of the chaperonin 60-chaperonin 10 complex requires the presence of MgATP, hydrolysis of ATP may not be required, since complex formation occurs in the absence of K+. The interaction of chaperonin 60 with unfolded or partly folded Rubisco does not require MgATP, K+, or chaperonin 10. However, discharge of the complex of chaperonin 60-Rubisco, which leads to the formation of active Rubisco dimers, requires chaperonin 10 and a coupled, K(+)-dependent hydrolysis of ATP. We propose that a role of chaperonin 10 is to couple the K(+)-dependent hydrolysis of ATP to the release of the folded monomers of the target protein from chaperonin 60.

Adenosine Triphosphatases↗